Transition-State Theory and Reaction Mechanism in Drug Action and Drug Design

  • James K. Coward


Rational development of potent and specific new drugs requires a detailed knowledge of the chemical mechanism of action for available pharmacologic agents and/or the enzymes which catalyze a drug-sensitive reaction. Numerous drugs now in the pharmacopeia have been discovered largely by serendipity and by testing thousands of analogs of known effective agents. However, the emergence of bioorganic chemistry has provided a mechanistic foundation on which medicinal chemists and pharmacologists can construct a detailed understanding of the mode of action of drugs currently available and can improve the design of new agents. In previous chapters of this book, others have presented detailed descriptions of the determination of transition-state structures and their role in biochemical reactions. In this chapter, the application of these concepts to understanding the mode of drug action and to the design of new drugs will be considered. The use of transition-state analogs and multisubstrate adducts as potent and specific chemotherapeutic agents (the theoretical aspects of which were described by Wolfenden in Chapter 15) will be presented as the logical extension of transition-state theory into pharmacology. The preceding chapters have dealt with phenomena for which there is a considerable amount of literature available. In this final chapter, we shall discuss an approach to the study of drug action and drug design about which there is very little in the literature. It is hoped that this brief presentation will stimulate others to attempt to bridge the gap between bioorganic chemistry and pharmacology.


Drug Design Dihydrofolate Reductase Thymidylate Synthetase Carbamyl Phosphate Aspartate Transcarbamylase 
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Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • James K. Coward
    • 1
  1. 1.Department of PharmacologyYale University School of MedicineNew HavenUSA

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